What is the first line treatment for a child presenting with jaundice, arthritis, rash, hyperbilirubinemia, and positive Immunoglobulin G (IgG) and autoantibodies?

First-Line Treatment for Pediatric Autoimmune Hepatitis

The first-line treatment is prednisone combined with azathioprine (option b). This clinical presentation—jaundice, arthritis, rash, hyperbilirubinemia, positive IgG, and autoantibodies—is characteristic of autoimmune hepatitis (AIH) in a child, and immediate immunosuppressive therapy is required.

Why Combination Therapy is First-Line

All children with confirmed AIH should receive immediate treatment with prednisone (1-2 mg/kg/day, maximum 60 mg/day) plus azathioprine (1-2 mg/kg/day), as this achieves remission in 75-90% of patients within 6-9 months while minimizing growth-impairing effects of prolonged high-dose corticosteroids alone. 1

• The combination of prednisolone plus azathioprine is explicitly stated as "conventional treatment" for both AIH and autoimmune sclerosing cholangitis in pediatric patients 2
• This regimen achieves complete remission in 67.6% of pediatric patients with partial remission in an additional 17.6% 3
• Prednisone with or without azathioprine represents the "milestone of therapy" and is proven effective in children 4

Why NOT the Other Options

NSAIDs (option c) have no role in treating AIH—they address only symptomatic arthralgia but do not treat the underlying immune-mediated liver destruction that will progress to cirrhosis without immunosuppression. 2

Plasma exchange (option a) is not indicated as first-line therapy for AIH. While it may be considered in acute liver failure scenarios unresponsive to medical therapy, the standard approach even in acute severe AIH is high-dose corticosteroids first. 5

Treatment Initiation Protocol

• Start prednisone at 1-2 mg/kg/day (maximum 60 mg/day) combined with azathioprine 1-2 mg/kg/day 1
• Azathioprine should be initiated when bilirubin is below 6 mg/dL (100 μmol/L), ideally starting at 50 mg/day and increasing based on response 2, 5
• In acute severe presentations, begin with high-dose intravenous corticosteroids (≥1 mg/kg/day) as early as possible 5

Expected Response and Monitoring

• Almost all children show improvement in liver enzymes within 2-4 weeks, with 80-90% achieving laboratory remission in 6-12 months 1
• Monitor AST, ALT, bilirubin, and IgG levels at 4-6 week intervals 1
• Serum aminotransferases should improve within 2 weeks of treatment initiation 2, 5

Tapering Strategy

• Taper prednisone over 6-8 weeks to reach maintenance dose of 0.1-0.2 mg/kg/day or 5 mg/day (whichever is higher) while keeping azathioprine at the same dose throughout 1
• Continue treatment for at least 2-3 years with normal liver tests and IgG for at least 1 year on low-dose therapy before considering withdrawal 1

Critical Pitfalls to Avoid

Do not delay treatment in children with AIH—more than 50% of pediatric patients present with cirrhosis already established, and the disease appears more aggressive at presentation than in adults. 1 Delays in treatment adversely affect long-term outcomes. 1

Do not use prednisone monotherapy as first-line unless there are specific contraindications to azathioprine (severe pre-treatment cytopenia, known TPMT deficiency, active malignancy, or pregnancy). 1 Monotherapy requires higher corticosteroid doses with greater growth-impairing effects. 1

Counsel families about high relapse rates—relapse after drug withdrawal occurs in 60-80% of children, substantially higher than the 50-90% rate in adults. 1 Retreatment is highly likely. 1

Special Considerations for Acute Severe Presentation

If this child has acute severe AIH (which the hyperbilirubinemia suggests):

• Assess response within 7 days—failure to improve serum bilirubin or clinical worsening within 7 days should prompt immediate listing for emergency liver transplantation while continuing corticosteroids 5
• High-dose intravenous corticosteroids should be initiated immediately at ≥1 mg/kg/day 5
• Azathioprine can be added after initial stabilization when bilirubin falls below 6 mg/dL 5

Long-Term Management

• Long-term azathioprine monotherapy (1-2 mg/kg/day) effectively maintains remission in children, allowing corticosteroid withdrawal with relapse rates of only 17.9% 1
• All children on long-term corticosteroids require calcium and vitamin D supplementation, bone mineral density monitoring, and regular blood count monitoring for azathioprine-related cytopenia 1
• Vaccinate against hepatitis A and B early in treatment 1